The present invention relates to a micropipette superior in droplet-volume controllability and productivity and preferably used to line and fix micro-volume droplets at a high density for applications such as manufacturing of DNA chips. The present invention further relates to a dispenser using the micropipette.
The genetic-structure analyzing method has been remarkably advancing recently, and many genetic structures, including structures of human genes, have been clarified. To analyze the above genetic structures, a DNA chip is used in which thousands to tens of thousands or more of different types of DNA pieces are lined and fixed as microspots on a substrate, such as a microscope slide glass.
As methods for forming microspots in manufacturing the DNA chip, the QUILL method, the pin-and-ring method, and the spring pin method are widely used. Even when any method is used, it is necessary to decrease the fluctuation of volumes and shapes of microspots and keep the distance between microspots constant. Moreover, it is greatly desired that a new method exhibiting superior shape controllability and productivity of microspots is developed to further increase the density.
In this case, the QUILL method is a method for forming a microspot by storing samples in a concave portion formed at the tip of a pin, and making the pin tip contact a substrate, thereby moving the samples in the concave portion onto the substrate. However, there is a problem with respect to durability in that the pin tip is deformed or damaged due to the contact with a substrate, or a problem in that cross contamination easily occurs due to imperfect cleaning of the samples stored in the concave portion.
The pin and ring method is a method for forming spots on a substrate by reserving a sample solution in a microplate with a ring and thereafter catching the sample in the ring with the tip of a pin so that the solution passes through the ring. However, the number of types of samples that can be reserved at one time depends on the number of rings, which has been limited so far. Therefore, to form microspots of thousands to tens of thousands of types of samples, hundreds to thousands of cleaning and drying steps are also necessary. Thus, productivity is not as high as would be desired.
The spring pin method is a method for forming microspots by pressing a sample attached to the tip of a pin against a substrate, thereby moving the sample onto the substrate, in which pin and substrate damage are moderated by a double-pin structure having a built-in spring to spout the sample. However, only one-time spotting can be performed by one-time reservation. Therefore, the method is inferior in productivity.
Furthermore, with these conventional microspot-forming methods, because each sample solution is carried onto a substrate while it is exposed to the atmosphere, trouble occurs in that the sample is dried while it is carried and spotting cannot be performed. Therefore, a problem occurs in that a very expensive sample solution cannot be efficiently used.
Furthermore, a method for performing spotting by using the so-called ink-jet system practically used for a printer was studied. However, forming thousands to ten thousands of samples in separate channels has many problems from viewpoints of size and cost. Moreover, in case of the ink-jet system, it is necessary to fill a pump with samples without any bubbles before spotting. It is necessary to use much of the sample to fill the pump and, therefore, sample use efficiency is inferior. Furthermore, it is better for bubble discharge that a liquid moves through a channel including a pump chamber, at a high speed, thereby being agitated in the channel. Thus, when a delicate DNA solution is used as a sample, DNA may be damaged.
The present invention has been made to solve the above problems, and its object is to provide a micropipette making it possible to form microspots at a high accuracy and a high speed and to provide a dispenser having superior productivity using the micropipette which is capable of forming microspots by efficiently dispensing hundreds to tens of thousands of different samples at one time.